Pathophysiological profiling of vocal fold hyperkeratosis

Project Summary/Abstract Vocal fold (VF) hyperkeratosis – an accumulation of epithelial surface keratin resulting in clinical leukoplakia – is primarily managed using destructive techniques that risk iatrogenic injury, fibrosis, and voice impairment. Given the potential morbidity of biopsy and lesion removal, there is a compelling need for new approaches to the workup and treatment of VF leukoplakic disorders that are non-destructive and grounded in disease pathophysiology. In the current application, we propose translational research that will advance this goal. Our preliminary data indicate that the essential nutrient vitamin A is a key regulator of epithelial health and that systemic vitamin A deficiency can directly contribute to hyperkeratosis. Based on evidence of vitamin A’s importance to VF stellate and epithelial cell biology, and its direct relevance to VF hyperkeratosis, we propose three Specific Aims that will advance this research area towards greater clinical applicability by: (i) assessing the systemic vitamin A status and lesion histopathology of patients with VF hyperkeratosis, and (ii) examining vitamin A trafficking to, and uptake by, normal and hyperkeratotic VF mucosa in a rat model. Our overarching goal is to determine if there is a pathophysiologic rationale for vitamin A supplementation in the treatment of VF hyperkeratosis. Such a therapy would be transformative – both as a first-line approach for patients who require conservative management, as well as an adjuvant therapy in patients for whom surgical treatment is indicated.